DESCRIPTION (Verbatim from Applicant's Abstract): Porcine bioprosthetic heart valves (PBHV) continue to fail from calcification and mechanical damage. We have demonstrated for PBHV that cyclic fatigue induces loss of radial compliance, tensile strength, and flexural rigidity. Clinically, about 85 percent of all PBHV fail with tearing, and some fail with little or no calcification. These and other studies demonstrate that while not a strict prerequisite for calcification, maintaining tissue structural integrity is a prime factor in inhibiting PBHV calcification and extending durability. Our long-term goal is the development of rigorous engineering principals for improving PBHV, based on a thorough understanding of tissue-and organ-level biomechanics. During the cardiac cycle cusps undergo large flexural displacements, subjecting the layers to alternating tensile and compressive stresses. Cuspal flexural rigidity, and hence the stresses during flexure, are substantially increased by chemical treatment. Since PBHV are fibrous composite materials, it is likely that they are very susceptible to compressive stress induced damage. We hypothesize that a major mechanism of PBHV failure is structural damage independent of calcification, resulting from high compressive stresses present in the chemically treated tissue extracellular matrix (ECM) during cuspal flexure. An in-depth understanding of the fatigue life behavior of the chemically treated porcine aortic valve cusp independent of PBHV design is a critical first step towards the development of novel chemical treatments that seek to mitigate the effects of structural damage. This will ultimately aid in the rational development, as opposed to the current ad-hoc approach, of novel chemically modified collagenous biomaterials for more durable PBHV. We will test our hypothesis with the following specific aims: 1. Determine how chemical treatment alters cuspal layer micromechanics. 2. Quantify PBHV cuspal deformation during the cardiac cycle. 3. Determine how long-term cyclic fatigue alters PBHV later structure and mechanical properties.